View clinical trials related to Invasive Pulmonary Aspergillosis.
Filter by:Brief Research Proposal: Non-Invasive Detection of Invasive Pulmonary Aspergillosis in ICU Patients Background: Invasive Pulmonary Aspergillosis (IPA) is a critical threat to patients in ICUs, especially those undergoing mechanical ventilation. Traditional diagnostic methods are invasive and carry risks. This study proposes a non-invasive, innovative approach utilizing galactomannan (GM) analysis in Exhaled Breath Condensate (EBC) for early IPA detection. Objective: To evaluate the diagnostic accuracy of measuring GM levels in EBC for detecting IPA in mechanically ventilated patients, comparing it against the conventional Bronchoalveolar Lavage Fluid (BALF)-GM measurements. Methods: A clinical trial will be conducted with 75 mechanically ventilated patients suspected of having IPA. The study will compare the effectiveness of EBC-GM levels against BALF-GM levels in diagnosing IPA, focusing on sensitivity, specificity, and diagnostic accuracy. The novel, self-designed EBC collection device will facilitate the safe and efficient collection of EBC from patients. Expected Outcomes: Validation of EBC-GM Diagnostic Accuracy: Anticipate demonstrating that EBC-GM levels provide a comparable diagnostic accuracy to BALF-GM, establishing a non-invasive, safer alternative for IPA detection. Implementation of a Non-Invasive Diagnostic Tool: The study aims to introduce a non-invasive diagnostic approach that can potentially replace more risky, invasive methods, improving patient care in ICUs. Contribution to Clinical Practice: By providing a new method for early and safer detection of IPA, the study is expected to influence clinical guidelines and practices in the management of critically ill, ventilated patients. Significance: This research has the potential to revolutionize the diagnosis of fungal infections in critically ill patients by offering a non-invasive, accurate, and safer diagnostic tool, thereby improving patient outcomes and reducing the risks associated with invasive diagnostic procedures.
The diagnosis of invasive pulmonary aspergillosis (IPA) bears grave implications for the prognosis and treatment plan of the immunosuppressed patient. Thus far, such diagnosis in the immunosuppressed patient, such as patients with acute myeloid leukemia (AML), relied heavily on chest computed tomography (CT) and bronchoalveolar lavage (BAL), an invasive approach bearing many caveats. Volatile organic compounds (VOC) are compounds that could be detected in exhaled air, and have shown some potential in the non-invasive diagnosis of various conditions, including IPA. In this prospective longitudinal study we aim to compare the VOC profiles of patients diagnosed with AML (baseline) to the profile of the same patient diagnosed with IPA later on, and to the post recovery profile in the same patient. This approach should resolve many of the issues plaguing prior attempts at VOC based IPA diagnosis, mainly the lack of properly designed controls. Samples will be collected from consenting patients using Tedlar bags, and analyzed using thermal desorption gas chromatography mass spectrometry (TD-GC-MS). VOCs detected will be digitally analyzed to construct different classification models, with predictive performances compared to the clinical diagnosis using the accepted methods will be assessed by binary logistic regression.
Voriconazole Inhalation Powder is available on an expanded access basis to patients with pulmonary aspergillosis for up to 12 weeks. Duration of treatment may be extended on a case-by-case basis depending on drug availability and after discussion with the Sponsor.
The last decade has seen a significant increase in secondary Aspergillus infections, not only due to primary hypersensitivity, and immunodeficiency based on oncological diseases and their therapy, but mainly due to a rise in severe respiratory infections (H1N1, COVID-19, bacterial infections). This is most evident in critically ill patients whose life is threatened by invasive pulmonary aspergillosis (IPA), with over 90 % of cases being caused by Aspergillus fumigatus. In recent decades, various biomarkers with well-known limits of use (Aspergillus DNA, galactomannan, 1,3-ß-D-glucan) have been used for early diagnosis of IPA. However, the clinical need to clearly distinguish the onset of IPA from colonization is much more significant. The current biomarkers only provide "probable IPA" interpretation, and the diagnosis is rarely confirmed. Based on our preliminary studies, the use of new low molecular weight substances (secondary metabolites) combined with acute-phase proteins (pentraxin 3) allows very reliable immediate confirmation of IPA. In tissue samples, bronchoalveolar lavage fluid, endotracheal aspirate, breath condensate, serum, and urine of critically ill patients, the investigators will be able to recognize and confirm IPA in time using highly sensitive mass spectrometry detecting specific microbial siderophores in correlation with a significantly increased concentration of acute-phase host protein (pentraxin 3) within hours of the beginning of the invasion of lung tissue. Through a prospective multicentre study, the investigators will evaluate the benefit of new biomarkers in non-invasive IPA confirmation, improve the IPA diagnostic algorithm and transfer the detection method to MALDI-TOF spectrometers widely used in Clinical laboratories in the Czech Republic. In MALDI-TOF mass spectrometry, the ion source is matrix-assisted laser desorption/ionization (MALDI), and the mass analyser is a time-of-flight (TOF) analyser. The study results will contribute to a high clarity of IPA cases, the accurate introduction of antifungal therapy, and a better prognosis of survival of critically ill patients.
Mechanically ventilated patients are at risk of developing ventilator-associated pneumonia (VAP). Invasive pulmonary aspergillosis (IPA), the diagnosis of which motivates the implementation of specific treatments, is one of the causes of VAP. The hypothesis of the study is that the incidence of IPA is 12.4%. For each patient presenting with a suspicion of VAP and requiring a bronchoalveolar lavage (BAL), the diagnosis of API will be evaluated by biological examinations performed on blood and BAL. Medical and surgical history as well as clinical and biological data will be collected for 28 days or until discharge from the ICU.
Many children and young people are at risk of invasive fungal disease (IFD), such as those who have had a haematopoietic stem cell transplants, those with an immune deficiency or those who are prescribed immunosuppressive drugs, for example, corticosteroids. One type of mould that causes invasive fungal disease is called Aspergillus. There is currently no quick test which can tell us if someone has an invasive fungal disease caused by Aspergillus called Aspergillosis. It is a difficult condition to diagnose and the results from the tests that are involved take days or weeks to come back. These tests including a few different blood tests, a scan of the lungs (CT scans) and taking fluid from inside the lungs/airway. A new test for Aspergillosis is the lateral flow device (LFD) assay. This is a rapid test which gives a result within minutes. It involves testing a sample of the fluid from the lungs/airway. This fluid can be obtained as part of the routine investigations for Aspergillosis. It has been shown to be a good and safe test in adults but the investigators do not know if it will be a valuable test in children and young people yet. The purpose of this study is to determine whether the LFD test can effectively diagnose Aspergillosis in children and young people.
To assess the safety and efficacy of nebulized PC945 in combination with systemic antifungal therapy for the treatment of refractory IPA
Invasive aspergillosis (IA) are difficult to diagnose in the ICU population, as the patients often do not present the conventional risks factors of immunocompromised patients (EORTC/MSG criteria). In the ICU population, patients often present other risk factors, such as cirrhosis, COPD, influenza and currently SARS-Cov2. The clinicians are thus currently missing precise criteria to distinguish colonization from IA in these patients, while they need to decide if an antifungal treatment is necessary or not. A new algorithm, entitled BM ASP ICU, based on investigators field experience and the scientific literature, which takes into account both EORTC/MSG criteria and a combination of fungal biomarkers, was proposed recently by Haman et al, Annals Intensive Care, 2021. Additional serological assays (immunoprecipitation and ELISA) showed since their interest, especially concerning SARS-Cov2 patients, a new population at risk of IA in the ICU, which emerged in the past months. The present study aims at prospectively implementing the BM ASP ICU algorithm during two years in the routine practice of six ICU units distributed in general and teaching hospitals situated northeast of France. The BM ASP ICU algorithm would be completed by serological assays aiming at assessing a sensitization towards Aspergillus fumigatus. The investigators plan to include 400 ICU patients at risk of IA; SARS-Cov2 patients will be part of the cohort. A weekly screening including culture of respiratory samples, galactomannan antigen, fungal qPCRS (targeting A. fumigatus), and A. fumigatus serology will be applied for all included patients. The performance (sensitivity and specificity, likelihood ratios) of each fungal biomarkers, alone and in combination with others, will be assessed, for all patients, and also within subgroups of patients with specific risk factors (such as SARS-Cov2 for example). These results should lead to solid understanding of which combination of tests is optimal to diagnose IA and thus to initiate appropriate antifungal treatment. the investigators hope that this study will result in improved survival rate of ICU patients with IA.
The aim of this research project is to compare the results of Aspergillus specific test methods Aspergillus Galactomannan Enzyme Immunoassay (GM-EIA), Aspergillus polymerase chain reaction (PCR), Aspergillus Galactomannan Lateral Flow Assay (LFA) from different respiratory tract secretions. The bronchoalveolar lavage (BAL) fluid and bronchial secretions (NBL) are compared in the same examination for each patient.
In this study, a new, non-invasive method for diagnosis of pulmonary aspergillosis (PA) will be tested in a clinical pilot project.